This application responds to the collaborative R34 mechanism co-sponsored by the National Center for Complementary and Alternative Medicine (NCCAM) and the National Institute of Mental Health (NIMH). We will evaluate the feasibility of adapting and testing Mindfulness-Based Stress Reduction (MBSR), a promising CAM treatment, for improving clinical outcomes and neurocognitive function in older adults with anxiety disorders or major depressive disorder (MDD) along with cognitive impairment. This project is important because these disorders are very common and cause cognitive impairment in older adults;together, these clinical and neurocognitive impairments are highly disabling and inadequately helped by existing treatments. Our treatment development proposal is based on well-known links in aging between a hyperactive hypothalamic-pituitary-adrenal (HPA) axis stress response and cognitive impairment. We have demonstrated that HPA axis hyperactivity is dependent on worry severity and is reversible with treatment, improving memory as well as clinical symptoms. These findings suggest that novel treatments that inhibit HPA axis hyperactivity in late-life mental disorders will remediate cognitive impairment. We have also shown that mindfulness-based interventions are acceptable, feasible, and reduce anxiety and depression in older adults. MBSR counteracts anxiety and depression by increasing mindfulness and decreasing worry and rumination;it also inhibits HPA axis hyperactivity, generating the hypothesis that MBSR can improve clinical symptoms and cognitive impairment in older adults with anxiety disorders and MDD via increased mindfulness, resulting in reduced worry/rumination and reducing the HPA axis stress response. We therefore propose to adapt and test MBSR for older adults with depression or anxiety and mood-related cognitive impairment. Phase 1 will pilot an MBSR protocol for depressed or anxious older adults with memory impairment or executive dysfunction, modify the intervention as needed, develop adherence and competency measurement, and test a control condition. Phase 2 (pilot RCT) will randomize 100 older adults to the MBSR protocol or a control condition and will examine feasibility. Anxiety and depressive symptoms and memory and executive function are outcomes;changes in mindfulness, worry/rumination, and cortisol are mediators. MBSR is a promising, novel treatment strategy for late-life anxiety disorders and MDD. We propose to develop the treatment while exploring putative psychological and biological mechanisms (mindfulness and neuroendocrine changes) underlying the treatment effect, giving this study clinical and scientific significance. PUBLIC HEALTH RELEVANCE: Chronic anxiety and depression lead to cognitive decline in older adults through the mechanism of HPA axis hyperactivity. This study proposes to use Mindfulness-Based Stress Reduction, a brief, easily implementable CAM intervention that is also a potent inhibitor of a hyperactive neuroendocrine stress response, to improve anxiety, depression, and cognition in older individuals.